The 20-volume set LNCS 15842-15861, together with the 4-volume set LNAI 15862-15865 and the 4-volume set LNBI 15866-15869, constitutes the refereed proceedings of the 21st International Conference on Intelligent Computing, ICIC 2025, held in Ningbo, China, during July 26-29, 2025.The 1206 papers presented in these proceedings books were carefully reviewed and selected from 4032 submissions. They deal with emerging and challenging topics in artificial intelligence, machine learning, pattern recognition, bioinformatics, and computational biology.